In vitro effects of sodium butyrate, a histone deacetylase inhibitor on canine mammary tumour subtypes

Abstract

Malignant canine mammary tumours (CMTs) are subdivided as carcinomas (C), sarcomas (S) and carcinosarcomas (CS) according to their histological type. Due to the varying responses to different treatments, novel therapeutic approaches are required. Sodium butyrate (NaBu) is the first histone deacetylase inhibitor and exhibits anti-cancer activity in different types of human cancers. However, no study is available in the literature evaluating the effects of NaBu on CMT cells. Therefore, for the first time, we aimed to investigate the in vitro efficacy of NaBu on three subtypes of CMT cells. Primary cells were isolated from neoplastic tissues of three dogs with CMT. Cell viability, apoptotic percentage and changes in the cell morphology, apoptosis-associated gene and protein expression levels were evaluated. Our findings showed that NaBu decreased the growth of the cells and increased the percentage of apoptosis in three subtypes of CMT cells. Additionally, NaBu treatment affected the expression levels of genes and proteins associated with apoptosis, especially in S cells. Our preliminary results, for the first time, revealed the efficacy of NaBu in CMT cells and the importance of the histological subtype in NaBu response. However, the molecular classification of CMT and the underlying mechanisms of the different NaBu responses should be further investigated.